Ferrous sulfate remodels the properties of sodium alginate-based hydrogel and facilitates the healing of wound infection caused by MRSA.

Frequent occurrence of wound infection caused by multiple-resistant bacteria (MRB) has posed a serious challenge to the current healthcare system relying on antibiotics. The development of novel antimicrobial materials with high safety and efficacy to heal wound infection is of great importance in combating this crisis. Herein, we prepared a promising antibacterial hydrogel by cross-linking ferrous ions (Fe2+) with the deprotonated carboxyl anion in sodium alginate (Na-ALG) to cure wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Interestingly, ferrous-modified Na-ALG (Fe-ALG) hydrogel demonstrated better properties compared to the traditional Na-ALG-based hydrogels, including injectability, self-healing, appropriate fluidity, high-water retention, potent MRSA-killing efficacy, and excellent biocompatibility. Importantly, the addition of Fe2+ enhances the antibacterial efficacy of the Na-ALG hydrogel, enabling it to effectively eliminate MRSA and accelerate the healing of antibiotic-resistant bacterial-infected wounds in a remarkably short period (10 days). This modification not only facilitates wound closure and fur generation, but also mitigates systemic inflammation, thereby effectively impeding the spread of MRSA to the lungs. Taken together, Fe-ALG hydrogel is a promising therapeutic material for treating wound infections by Staphylococcus aureus, especially by antibiotic-resistant strains like MRSA.

Vitexin promotes the anti-senescence effect via inhibiting JAK2/STAT3 in D-Galactose-induced progeria mice and stress-induced premature senescence.

Vitexin is a natural flavonoid glycoside compound extracted from the leaves and seeds of Vitex negundo. It is widely distributed in the leaves and stems of numerous plants and exhibites remarkable anti-tumor, anti-inflammatory, and anti-hypertensive properties. However, whether vitexin presents the anti-aging and senescence prevention effect has not been fully elucidated. The purpose of this study is to investigate the effect of vitexin on progeria mice and cellular senescence, as well as its underlying molecular mechanisms. To generate a premature aging/senescence model in vivo and in vitro, we used D-galactose (D-gal), hydrogen peroxide (H2O2), and adriamycin (ADR), respectively. Our findings demonstrated that vitexin potentially delays D-gal-induced progeria mice; similar effects were observed in stress-induced premature senescent fibroblasts in culture. Interestingly, this effect of vitexin is closely correlated with the reduction of the senescence-associated secretory phenotype (SASP) and the inhibition of the SASP-related JAK2/STAT3 pathway. Furthermore, we determined that vitexin meets the pharmacological parameters using the freely available ADMET web tool. Collectively, our findings demonstrate that vitexin possesses anti-senescence and anti-aging properties due to the inhibition of SASP and suppression of JAK2/STAT3 signaling pathway.

E3 Ubiquitin Ligase NEDD4L Negatively Regulates Skin Tumorigenesis by Inhibiting IL-6/GP130 Signaling Pathway.

IL-6 signaling plays a crucial role in the survival and metastasis of skin cancer. NEDD4L acts as a suppressor of IL-6 signaling by targeting GP130 degradation. However, the effects of the NEDD4L-regulated IL-6/GP130 signaling pathway on skin cancer remain unclear. In this study, protein expression levels of NEDD4L and GP130 were measured in tumor tissues from patients with cutaneous squamous cell carcinoma. Skin tumors were induced in wild-type and Nedd4l-knockout mice, and activation of the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway was detected. The results indicated a negative correlation between the protein expression levels of NEDD4L and GP130 in cutaneous squamous cell carcinoma tissues from patients. Nedd4l deficiency significantly promoted 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin tumorigenesis and benign-to-malignant conversion by activating the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway, which was abrogated by supplementation with the GP130 inhibitor SC144. Furthermore, our findings suggested that NEDD4L can interact with GP130 and promote its ubiquitination in skin tumors. In conclusion, our results indicate that NEDD4L could act as a tumor suppressor in skin cancer, and inhibition of GP130 could be a potential therapeutic method for treating this disease.

Aged AßPPswe/PS1ΔE9 mice as a useful animal model for studying the link between immunological senescence and diseases.

The APPswe/PS1ΔE9 mouse is a double transgenic murine model that harbors two transgenes for Alzheimer's Disease (AD)-related mutant proteins. We previously discovered that this double transgenic animal had a premature immunosenescence phenotype. However, it is unclear how this phenotype progresses to a later stage. This study aimed to elucidate the changes in systemic characteristics aside from those associated with AD between elderly APPswe/PS1ΔE9 mice and littermate control wild-type mice. Tumors in all organs were considerably more frequent in AD mice aged 24 months than in the control wild-type mice. In addition, the survival rate of aged AD mice was considerably lower than that of wild-type control mice. Further, we discovered that the phenotypic difference was mainly caused by severe immunological aging, as evidenced by a high proportion of exhausted T lymphocytes in AD mice compared to wild-type mice of the same age. Based on our findings, the harm produced by normal aging is not as severe as immunological senescence. Addressing immunological aging, as opposed to anti-aging alone, may be a more crucial target for a long life free of cancer.

SerpinA3N Regulates the Secretory Phenotype of Mouse Senescent Astrocytes Contributing to Neurodegeneration.

Senescent astrocyte accumulation in the brain during normal aging is a driver of age-related neurodegenerative diseases such as Alzheimer's disease. However, the molecular events underlying astrocyte senescence in Alzheimer's disease are not fully understood. In this study, we demonstrated that senescent astrocytes display a secretory phenotype known as the senescence-associated secretory phenotype (SASP), which is associated with the upregulation of various proinflammatory factors and the downregulation of neurotrophic growth factors (eg, NGF and BDNF), resulting in a decrease in astrocyte-mediated neuroprotection and increased risk of neurodegeneration. We found that SerpinA3N is upregulated in senescent primary mouse astrocytes after serial passaging in vitro or by H2O2 treatment. Further exploration of the underlying mechanism revealed that SerpinA3N deficiency protects against senescent astrocyte-induced neurodegeneration by suppressing SASP-related factors and inducing neurotrophic growth factors. Brain tissues from Alzheimer's disease model mice possessed increased numbers of senescent astrocytes. Moreover, senescent astrocytes exhibited upregulated SerpinA3N expression in vitro and in vivo, confirming that our cell model recapitulated the in vivo pathology of these neurodegenerative diseases. Altogether, our study reveals a novel molecular strategy to regulate the secretory phenotype of senescent astrocytes and implies that SerpinA3N and its regulatory mechanisms may be potential targets for delaying brain aging and aging-related neurodegenerative diseases.

Ferric chloride induces ferroptosis in Pseudomonas aeruginosa and heals wound infection in a mouse model.

BACKGROUND: Pseudomonas aeruginosa is one of the most common pathogens that lead to fatal human infection. This Gram-negative pathogen has evolved complex drug resistance, which poses significant challenges to the current antibiotic-dependent healthcare system. New therapeutic approaches are urgently required to treat infections caused by P. aeruginosa. METHODS: Inspired by ferroptosis, the antibacterial effects of iron compounds on P. aeruginosa via direct exposure were investigated. In addition, thermal-responsive hydrogels to carry FeCl3 were developed as a wound dressing to treat P. aeruginosa-induced wound infection in a mouse model. RESULTS: The results showed that 200 µM FeCl3 killed more than 99.9% of P. aeruginosa cells. FeCl3-mediated cell death in P. aeruginosa was associated with hallmarks of ferroptosis in mammalian cells, including reactive oxygen species (ROS) burst, lipid peroxidation, and DNA damage. Catalase or Fe2+ chelator alleviated FeCl3-mediated cell death, indicating that H2O2 and labile Fe2+ induced the Fenton reaction leading to cell death. Further proteomics analysis showed that proteins related to glutathione (GSH) synthesis and the glutathione peroxidase (GPX) family were significantly downregulated after FeCl3 treatment, which is equivalent to GPX4 inactivation in mammalian cells. The therapeutic effect of FeCl3 on P. aeruginosa was further evaluated in a mouse wound infection model using polyvinyl alcohol-boric acid (PB) hydrogels as a carrier of FeCl3. FeCl3-PB hydrogels completely cleared pus on wounds and promoted wound healing. CONCLUSION: These results indicated that FeCl3 induces microbial ferroptosis in P. aeruginosa and has high therapeutic potential for the treatment of P. aeruginosa wound infection.

Involvement of Paired Immunoglobulin-Like Receptor B in Cognitive Dysfunction Through Hippocampal-Dependent Synaptic Plasticity Impairments in Mice Subjected to Chronic Sleep Restriction.

Sleep loss is often associated with cognitive dysfunction. Alterations in the structure and function of synapses in the hippocampus are thought to underlie memory storage. Paired immunoglobulin-like receptor B (PirB) plays a negative role in various neurological diseases by inhibiting axon regeneration and synaptic plasticity. However, the contributions of PirB to the mechanisms underlying the changes in synaptic plasticity after sleep loss that ultimately promote deficits in cognitive function have not been well elucidated. Here, we showed that chronic sleep restriction (CSR) mice displayed cognitive impairment and synaptic deficits accompanied by upregulation of PirB expression in the hippocampus. Mechanistically, PirB caused the dysregulation of actin through the RhoA/ROCK2/LIMK1/cofilin signalling pathway, leading to abnormal structural and functional plasticity, which in turn resulted in cognitive dysfunction. PirB knockdown alleviated synaptic deficits and cognitive impairment after CSR by inhibiting the RhoA/ROCK2/LIMK1/cofilin signalling pathway. Moreover, we found that fasudil, a widely used ROCK2 inhibitor, could mimic the beneficial effect of PirB knockdown and ameliorate synaptic deficits and cognitive impairment, further demonstrating that PirB induced cognitive dysfunction after CSR via the RhoA/ROCK2/LIMK1/cofilin signalling pathway. Our study sheds new light on the role of PirB as an important mediator in modulating the dysfunction of synaptic plasticity and cognitive function via the RhoA/ROCK2/LIMK1/cofilin signalling pathway, which indicated that hippocampal PirB is a promising therapeutic target for counteracting cognitive impairment after CSR. This illustration depicts the signalling pathway by PirB in mediating cognitive impairment and synaptic deficits in CSR mice. In the hippocampus of CSR mice, the expression level of PirB was significantly increased. In addition, CSR increases RhoA and ROCK2 levels and reduces levels of both LIMK1 and cofilin phosphorylation. PirB knockdown reverses cognitive impairment and synaptic plasticity disorders caused by CSR through the RhoA/ROCK2/LIMK1/cofilin signalling pathway.

TAT-LBD-Ngn2-improved cognitive functions after global cerebral ischemia by enhancing neurogenesis.

BACKGROUND: Stroke is the major cause of adult neurocognitive disorders (NCDs), and presents a significant burden on both of the families and society. To improve the cerebral injury, we generated a blood-brain barrier penetrating peptide TAT-LBD-Ngn2, in which Ngn2 (Neurogenin2) is a classical preneural gene that enhances neurogenesis, and neural precursor cells survival and differentiation. We previously demonstrated that it has a short-term protective effect against cerebral ischemia-reperfusion injury. However, it is uncertain if TAT-LBD-Ngn2 could promote neurogenesis to exhibit long-term therapeutic impact. METHODS AND RESULTS: In present study, TAT-LBD-Ngn2 was administered for 14 or 28 days following bilateral common carotid arteries occlusion (BCCAO). After confirming that TAT-LBD-Ngn2 could cross the brain blood barrier and aggregate in the hippocampus, we conducted open field test, Morris water maze and contextual fear conditioning to examine the long-term effect of TAT-LBD-Ngn2 on cognition. We discovered that TAT-LBD-Ngn2 significantly improved the spatial and contextual learning and memory on both days 14 and 28 after BCCAO, while TAT-LBD-Ngn2 exhibited anxiolytic effect only on day 14, but had no effect on locomotion. Using western blot and immunofluorescence, TAT-LBD-Ngn2 was also shown to promote neurogenesis, as evidenced by increased BrdU+ and DCX+ neurons in dentate gyrus. Meanwhile, TAT-LBD-Ngn2 elevated the expression of brain derived neurotrophic factor rather than nerve growth factor compared to the control group. CONCLUSIONS: Our findings revealed that TAT-LBD-Ngn2 could dramatically promote learning and memory in long term by facilitating neurogenesis in the hippocampus after global cerebral ischemia, indicating that TAT-LBD-Ngn2 may be an appealing candidate for treating poststroke NCD.

Complete mitochondrial genome of Mastigias papua (Scyphozoa: Rhizostomeae: Mastigiidae) based on next-generation sequencing and phylogenetic analysis.

We assembled the complete mitochondrial genome (mitogenome) of Mastigias papua (Scyphozoa: Rhizostomeae: Mastigiidae) by the data generated from the next-generation sequencing platform. The complete mitogenome of M. papua was 16,560 bp in length, containing 14 protein-coding genes, two transfer RNA genes, and two ribosomal RNA genes. The base compositions were A 30.65%, C 15.16%, G 16.34%, and T 37.86%, with a gene arrangement similar to the mitogenomes derived from other representatives of Scyphozoa. Based on the 13 common protein-coding genes of 16 species within Scyphozoa, we constructed the phylogenetic tree and found that M. papua has a close relationship with Cassiopea andromeda and Cassiopea xamachana. All these species belong to an order of jellyfish Rhizostomeae, which have similar morphological characteristics. This is agreement with the conclusion we got by the phylogenetic relationship analysis using molecular data. This research has practical implications for advancing understanding of the phylogenetic relationships, taxonomic classifications, and phylogeography within Scyphozoa.

The Roles of Ciliary Neurotrophic Factor - from Neuronutrition to Energy Metabolism.

Ciliary neurotrophic factor (CNTF) is a pluripotent neurotrophic factor originally isolated from chicken embryo ciliary neurons. It has a powerful role in developing and maintaining the optic nervous system and has been used for many vision-related diseases. It also plays an important role in the neurogenesis, regeneration and survival of other neurons, including neural stem cells, dorsal root ganglion, sensory neurons and motor neurons. CNTF is related to neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. In addition to its role in the nervous system, CNTF regulates the balance of energy metabolism and the administration of CNTF induces body weight loss. More CNTF functions have been found with the deepening of study, such as protecting and promoting cardiomyocyte proliferation. In addition, CNTF even participates in mental illness and inflammation suppressing. CNTF exerts multidirectional physiological activity by regulating the transcription of various genes through a variety of signalling pathways (including JAK/STAT, MAPK, and PI3K/AKT). This review summarizes the roles and mechanisms of CNTF in the optic nervous system, retinal-related diseases, neuronal protection, and especially nutrition, energy metabolism and other aspects.

Rapid and highly specific detection of site-specific 5-hydroxymethylcytosine based on peroxotungstate oxidation and mismatch ligation-based LAMP.

We have developed a rapid and specific method for site-specific 5-hydroxymethylcytosine (5hmC) quantification at single-base resolution. This bisulfite-free method integrates the peroxotungstate oxidization with the mismatched probe-assisted ligation to guarantee the specificity. Moreover, the high-efficiency LAMP also makes the proposed method suitable for the detection of low-content samples.

Integrated gene co-expression network analysis reveals unique developmental processes of Aurelia aurita.

The typical life cycle of the moon jellyfish (Aurelia aurita) includes the planula, polyp, strobila, ephyra, and medusa developmental stages. These stages exhibit huge differences in both external morphology and internal physiological functions. However, the gene co-expression network involved in these post-embryonic developmental processes has not been studied yet. Here, based on 15 RNA sequencing samples covering all five stages of the A. aurita life cycle, we systematically analyzed the gene co-expression network and obtained 35 relevant modules. Furthermore, we identified the highly correlated modules and hub genes for each stage. These hub genes are implicated to play important roles in the developmental processes of A. aurita, which should help improve our understanding of the jellyfish life cycle.

Amyloid-beta Targeted Therapeutic Approaches for Alzheimer's Disease: Long Road Ahead.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment and cognitive decline. The obvious pathological features of AD are still amyloid plaques and neurofibrillary tangles. Development of disease-modifying treatments for AD has been challenging, with almost all drugs aborted. The amyloid cascade concept has been questioned due to the failures of various amyloid-targeting prospects. Despite this, targeting amyloid-ß (Aß) active immunotherapy provided some positive results to support this hypothesis and clinical trials of these candidates are ongoing. In this review, we describe the latest advance in therapeutic strategies based on amyloidogenic processing and evaluate the pros and cons of each treatment strategy. We also highlight the current status of the hottest immunotherapy and discuss the future development direction.

Hydroxyapatite formation in biomimetic synthesis with the interface of a pDA@SIS membrane.

Porcine decellularized small intestine submucosa (SIS) is a collagen membrane, which offers great potential as an organic substrate template in mineralization processes due to its good biodegradability and biocompatibility. However, a long period of mineralization and low efficiency are apparent, and the mechanism of collagen fiber mineralization has often been neglected in the previous literature. Thus, in this paper, we present a novel model of biomimetic collagen mineralization which uses dopamine (DA) molecules with the activating and retouching function of SIS collagen membranes and regulating collagen mineralization to construct the structure of mineralized collagen hard tissues. The crystal biomimetic mineralization growth of calcium phosphate on membranes is studied in different solid-liquid interfaces with a double ion self-assembled diffusion system under the simulated physiological microenvironment. In the system, pDA@SIS membranes are used to control the concentration of Ca2+ and PO4 3- ionic diffusion to generate supersaturation reaction conditions in 1-14 days. The system can successfully obtain polycrystals with low crystallinity on the pDA-collagen complex template surface of collagen fibers and along the collagen fibers. It initiates a generalized bionic mineralization pathway which can reduce the nucleation interfacial energy to promote rapid hydroxyapatite (HAP) nucleation and crystallization and accelerate the rate of collagen fiber mineralization. The pDA@SIS mineralized collagen membrane shows good biocompatibility with 100% cellular activity in the CCK-8 test, which significantly improved the adhesion proliferation of MC3T3-E1 cells. The pDA-SIS collagen complex, as a new type of mineralization template, may propose a new collagen mineralization strategy to produce a mineralized pDA@SIS scaffold bone-like material for tissue engineering or can potentially be applied in bone repair and regeneration.

Potential Regulators of the Senescence-Associated Secretory Phenotype During Senescence and Aging.

Senescent cells express and secrete a variety of extracellular modulators that include cytokines, chemokines, proteases, growth factors, and some enzymes associated with extracellular matrix remodeling, defined as the senescence-associated secretory phenotype (SASP). SASP reinforces senescent cell cycle arrest, stimulates and recruits immune cells for immune-mediated clearance of potentially tumorigenic cells, limits or induces fibrosis, and promotes wound healing and tissue regeneration. On the other hand, SASP mediates chronic inflammation leading to the destruction of tissue structure and function and stimulating the growth and survival of tumor cells. SASP is highly heterogeneous and the role of SASP depends on the context. The regulation of SASP occurs at multiple levels including chromatin remodeling, transcription, mRNA translation, intracellular trafficking, and secretion. Several SASP modulators have already been identified setting the stage for future research on their clinical applications. In this review, we summarize in detail the potential signaling pathways that trigger and regulate SASP production during aging and senescence.

L22 ribosomal protein is involved in dynamin-related protein 1-mediated gastric carcinoma progression.

Mitochondrial fission depends on dynamin-related protein 1 (Drp1) guanosine triphosphatase activity. Although there is some association between Drp1 and gastric cancer, the detailed mechanism remains largely unknown. In this study, the elevation of Drp1 was observed in human gastric carcinoma specimens including gastric mixed adenocarcinoma tissues, gastric intestinal-type adenocarcinoma tissues, and human gastric cancer cells compared to normal control, but not in diffuse gastric adenocarcinoma tissues. Gastric cancer patients with high Drp1 harbored advanced pathological stages and poor progression-free survival probability compared to those with low Drp1. Mdivi-1-mediated inactivation of Drp1 robustly inhibited cell viability and tumor growth but conversely induced cell apoptotic events in vitro and in vivo. Based on the Encyclopedia of RNA Interactomes Starbase, L22 ribosomal protein (RPL22) was recognized as the potential downstream oncogene of Drp1. Clinically, the significant correlation of Drp1 and RPL22 was also verified. Mechanistically, Drp1 inactivation did not affect the accumulation of RPL22 in gastric carcinoma. However, the intracellular distribution of RPL22 had an endonuclear location in Drp1-inactivated tumors. Of note, Drp1 inactivation notably reduced the expression of cytoplasmic RPL22 and increased its nuclear level in gastric cancer cells. Collectively, Drp1 had high levels in human gastric carcinoma specimens and could serve as a potential diagnostic and prognostic biomarker in gastric carcinoma. The Drp1 inactivation-mediated anti-proliferative and pro-apoptosis effects on gastric cancer were possibly associated with nuclear import of RPL22. This knowledge may provide new therapeutic tools for treating gastric carcinoma via targeting mitochondria-related ribosome pathway.

Next-generation sequencing yields the complete mitochondrial genome of Pterygoplichthys pardalis (Loricariidae; Siluriformes).

In this study, we report the complete mitochondrial genome of Pterygoplichthys pardalis has derived by next-generation sequencing. The complete mitochondrial genome of P. pardalis contains 16,425 bp encompassing 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and one control region (D-loop). The base composition is A 31.79%, C 26.89%, G 14.63%, and T 26.69%, and its gene arrangement is consistent with mitochondrial genomes derived from other representatives of Loricariidae. A phylogenetic tree of 24 Loricariidae species constructed based on the 13 coding genes shows that P. pardalis is clustered with other Pterygoplichthys genus. It suggests that the molecular classification results confirm its external morphological characteristics. These results have reference value for the further study of phylogenetic relationship, taxonomic classification, and phylogeography of Loricariidae.

Secreted Frizzled Related Proteins in Cardiovascular and Metabolic Diseases.

Abnormal gene expression and secreted protein levels are accompanied by extensive pathological changes. Secreted frizzled related protein (SFRP) family members are antagonistic inhibitors of the Wnt signaling pathway, and they were recently found to be involved in the pathogenesis of a variety of metabolic diseases, which has led to extensive interest in SFRPs. Previous reports highlighted the importance of SFRPs in lipid metabolism, obesity, type 2 diabetes mellitus and cardiovascular diseases. In this review, we provide a detailed introduction of SFRPs, including their structural characteristics, receptors, inhibitors, signaling pathways and metabolic disease impacts. In addition to summarizing the pathologies and potential molecular mechanisms associated with SFRPs, this review further suggests the potential future use of SFRPs as disease biomarkers therapeutic targets.

Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer Cells via ERK/JNK Pathway.

BACKGROUND: Suppression of tumorigenicity 5 (ST5) has been considered as a tumor suppressor gene in HeLa tumor cells. However, its role in the progression of breast cancer remains vague. METHODS: Online database analysis was determined by Oncomine and Breast Cancer Gene-Expression Miner v4.4 (bc-GenExMiner v4.4). Tumor biology behaviors were measured by MTT assay, wound healing model, Transwell and Flow cytometry assays. Methylation-specific PCR (MSP) was employed to detect promoter methylation. RESULTS: Low level of ST5 was observed in breast cancer specimens, particularly in recurrent, invasive breast cancer cases compared to para-carcinoma tissue or non-invasive breast cancer. The downregulation of ST5 was also proved in MDA-MB-231 and SKBR3 cell lines with a high invasive capability as compared to MCF-7 cell with a low invasive capability. ST5 was negatively associated with pathological stages of breast cancer. ST5-downregulation promoted, while ST5-upregulation inhibited the progression of cell proliferation, cell cycle and migration of MDA-MB-231 cells. Additionally, ST5 knockdown inhibited, whereas ST5 overexpression promoted apoptosis of MDA-MB-231 cells. However, ST5 modification, either upregulation or downregulation, had no significant impact on tumor behaviors of MCF-7 cells. Mechanistically, ST5 protein ablation activated, while ST5-upregulation repressed the activities of phosphorylated ERK1/2 and JNK, and subsequently the expression of c-Myc. PD98059-mediated ERK1/2 inhibition abolished the stimulatory effects of ST5-depletion on ERK1/2/JNK/c-Myc signaling axis, and ST5 depletion-mediated cell over-proliferation and migration. Of note, ST5 reduction in invasive breast cancer cells should implicate in the hypermethylation of ST5 promoter region. CONCLUSION: Our findings suggest that ST5 potentially acts as a tumor suppressor gene in invasive breast cancer through regulating ERK/JNK signaling pathway and provide a novel insight for breast cancer treatment.